In vitro degradation rate of apatitic calcium phosphate cement with incorporated PLGA microspheres

Calcium phosphate cements (CPCs) are frequently used as bone substitute material. Despite their superior clinical handling and excellent biocompatibility, they exhibit poor degradability, which limits bone ingrowth into the implant. Microspheres were prepared from poly(d,l-lactic-co-glycolic acid) (PLGA) and included in injectable CPCs as porogens in order to enhance its macroporosity after the polymeric microspheres had degraded. Upon degradation of the PLGA microspheres, acid is produced that enhances the dissolution rate of the CPC. However, the effect of the characteristics of PLGA microspheres on the degradation rate of CPCs has never been studied before. Therefore, the purpose of the current study was to investigate the dependence of CPC degradation on the chemical and morphological characteristics of incorporated PLGA microspheres. With respect to the chemical characteristics of the PLGA microspheres, the effects of both PLGA molecular weight (5, 17 and 44kDa) and end-group functionalization (acid-terminated or end-capped) were studied. In addition, two types of PLGA microspheres, differing in morphology (hollow vs. dense), were tested. The results revealed that, although both chemical parameters clearly affected the polymer degradation rate when embedded as hollow microspheres in CPC, the PLGA and CPC degradation rates were mainly dependent on the end-group functionalization. Moreover, it was concluded that dense microspheres were more efficient porogens than hollow ones by increasing the CPC macroporosity during in vitro incubation. By combining all test parameters, it was concluded that dense PLGA microspheres consisting of acid-terminated PLGA of 17kDa exhibited the highest and fastest acid-producing capacity and correspondingly the highest and fastest amount of porosity. In conclusion, the data presented here indicate that the combination of dense, acid-terminated PLGA microspheres with CPC emerges as a successful combination to achieve enhanced apatitic CPC degradation.     

Introduction of gelatin microspheres into an injectable calcium phosphate cement

For tissue engineered bone constructs, calcium phosphate cement (CPC) has a high potential as scaffold material because of its biocompatibility and osteoconductivity. However, in vivo resorption and tissue ingrowth is slow. To address these issues, microspheres can be incorporated into the cement, which will create macroporosity after in situ degradation. The goal of this study was to investigate the handling properties and degradation characteristics of CPC containing gelatin microspheres. Setting time and injectability were determined and an in vitro degradation study was performed. Samples were assayed on mass, compression strength, E-modulus, and morphology. A supplementary degradation test with gelatin microspheres was performed to investigate the influence of physical conditions inside the cement on microsphere stability. The gelatin microsphere CPCs were easy to inject and showed initial setting times of less than 3 min. After 12-weeks in vitro degradation no increase in macroporosity was observed, which was supported by the small mass loss and stabilizing mechanical strength. Even a clear densification of the composite was observed. Explanations for the lack of macroporosity were recrystallization of the cement onto or inside the gelatin spheres and a delayed degradation of gelatin microspheres inside the scaffold. The supplementary degradation test showed that the pH is a factor in the delayed gelatin microsphere degradation. Also differences in degradation rate between types of gelatin were observed. Overall, the introduction of gelatin microspheres into CPC renders composites with good handling properties, though the degradation characteristics should be further investigated to generate a macroporous scaffold.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

Incorporation of biodegradable electrospun fibers into calcium phosphate cement for bone regeneration

Inherent brittleness and slow degradation are the major drawbacks for the use of calcium phosphate cements (CPCs). To address these issues, biodegradable ultrafine fibers were incorporated into the CPC in this study. Four types of fibers made of poly(ε-caprolactone) (PCL) (PCL12: 1.1 μm, PCL15: 1.4 μm, PCL18: 1.9 μm) and poly(l-lactic acid) (PLLA4: 1.4 μm) were prepared by electrospinning using a special water pool technique, then mixed with the CPC at fiber weight fractions of 1%, 3%, 5% and 7%. After incubation of the composites in simulated body fluid for 7 days, they were characterized by a gravimetric measurement for porosity evaluation, a three-point bending test for mechanical properties, microcomputer topography and scanning electron microscopy for morphological observation. The results indicated that the incorporation of ultrafine fibers increases the fracture resistance and porosity of CPCs. The toughness of the composites increased with the fiber fraction but was not affected by the fiber diameter. It was found that the incorporated fibers formed a channel-like porous structure in the CPCs. After degradation of the fibers, the created space and high porosity of the composite cement provides inter-connective channels for bone tissue in growth and facilitates cement resorption. Therefore, we concluded that this electrospun fiber-CPC composite may be beneficial to be used as bone fillers.     

含锶磷酸钙骨水泥体内降解性能

目的评价含锶磷酸钙骨水泥（SrCPC）体内降解性能，比较含锶磷酸钙骨水泥与普通磷酸钙骨水泥（CPC）的降解率。方法新西兰大白兔15只随机编为1～15号。锶含量分别为0％、1％、5％和10％4种含锶磷酸钙骨水泥编为A、B、C和D组，将充分干燥至恒重的4种骨水泥试样分别植入到新西兰兔的背部脊柱两侧4个区域肌肉内。于术后4、8、12周各处死5只动物，取出试样清洗干燥至恒重后在电子天平上称重，计算出试样的失重量和失重率并方差分析。结果4周时，含10％锶的试样的降解率最高，其次是含5％锶的试样，不含锶的试样与含1％锶的试样的降解率较低且两者间无统计学意义；8周时，含10％锶的试样与含5％锶的试样的降解率无统计学意义，含1％锶的试样与不含锶的试样的降解率较低且两者间亦无统计学意义；12周时，含10％锶的试样的降解率为30％，含5％锶试样的降解率为26％，含1％锶的试样与不含锶的试样的降解率分别为18．88％和16．25％。结论锶含量在5％～10％之间的SrCPC在体内的降解速度要明显地快于CPC。     

Cell seeding into calcium phosphate cement

To improve the effectiveness of calcium phosphate cement (CPC), we have developed a method to seed osteoblasts into the cement. CPC powder is mixed with water to form a paste that can be shaped to fit a bone defect in situ. The paste hardens in 30 min, reacts to form hydroxyapatite, and is replaced with new bone. Reacted CPC is biocompatible but unreacted CPC paste was found to have toxic effects when placed on cell monolayers (MC3T3-E1 cells). In contrast, when cells were indirectly exposed to CPC paste using a porous membrane or by placing a coverslip containing adherent cells onto a bed of CPC paste, the unreacted CPC was nontoxic. These results suggested that gel encapsulation of the cells might protect them from the CPC paste. Thus, cells were encapsulated in alginate beads (3.6-mm diameter), mixed with CPC paste, and incubated overnight. Both vital staining (calcein-AM and ethidium homodimer-1) and the Wst-1 assay (measures dehydrogenase activity) showed that cell survival in alginate beads that were mixed with CPC was similar to survival in untreated control beads. These results suggest that gel encapsulation could be used as a mechanism to protect cells for seeding into CPC.     

Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles

In this study, the mechanical properties of an implanted calcium phosphate (CaP) cement incorporated with 20wt% poly (dl-lactic-co-glycolic acid) (PLGA) microparticles were investigated in a rat cranial defect. After 2, 4 and 8 weeks of implantation, implants were evaluated mechanically (push-out test) and morphologically (Scanning Electron Microscopy (SEM) and histology). The results of the push-out test showed that after 2 weeks the shear strength of the implants was 0.44+/-0.44MPa (average+/-sd), which increased to 1.34+/-1.05MPa at 4 weeks and finally resulted in 2.60+/-2.78MPa at 8 weeks. SEM examination showed a fracture plane at the bone-cement interface at 2 weeks, while the 4- and 8-week specimens created a fracture plane into the CaP/PLGA composites, indicating an increased strength of the bone-cement interface. Histological evaluation revealed that the two weeks implantation period resulted in minimal bone ingrowth, while at 4 weeks of implantation the peripheral PLGA microparticles were degraded and replaced by deposition of newly formed bone. Finally, after 8 weeks of implantation the degradation of the PLGA microparticles was almost completed, which was observed by the bone ingrowth throughout the CaP/PLGA composites. On basis of our results, we conclude that the shear strength of the bone-cement interface increased over time due to bone ingrowth into the CaP/PLGA composites. Although the bone-cement contact could be optimized with an injectable CaP cement to enhance bone ingrowth, still the mechanical properties of the composites after 8 weeks of implantation are insufficient for load-bearing purposes.     

In vivo behavior of a novel injectable calcium phosphate cement compared with two other commercially available calcium phosphate cements

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CPC). The novel cement was compared with two other commercially available CPCs. After mixing the powder and liquid phase, the CPCs were injected as a paste into a rabbit distal femoral defect model. The CPCs were evaluated after 24 h, 6 weeks, 26 weeks, and 52 weeks. The novel CPC was easy to handle and was fast setting. X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometry (FTIR) at the different implantation periods showed that the cement had converted to carbonated hydroxyapatite and remained stable over time. Histological evaluation showed bone apposition on the cement surface without any inflammatory response or fibrous encapsulation. At later time points, all CPCs were completely covered by a thin layer of bone. Osteoclast-like cells present at the interface resorbed parts of the cement mass. Histological and histomorphometrical analyses did not show any significant differences between the three implanted CPCs. The results indicate that the investigated CPC is biocompatible, osteoconductive, as well as osteotransductive and seems to be both biologically safe and effective as a bone void filler.     

N-乙酰半胱氨酸丝素微球复合磷酸钙骨水泥的制备及表征

BACKGROUND: Calcium phosphate bone cement has been applied to clinical surgery because of its good biocompatibility and osteoconduction. However poor mechanical properties and lack of osteoinductivity limit its wide application. OBJECTIVE: To develop calcium phosphate cement incorporated with N-acetylcysteine (NAC) loaded silk fibroin microspheres (SFM), which is a kind of new injectable bone graft material with slow-release function, and evaluate its physical and chemical properties and cell compatibility. METHODS: Empty SFMs were prepared with emulsion solvent evaporation to absorb NAC solution of different concentrations by NAC-SFM and the concentration of NAC at the maximum drug loading ratio was determined. Then, NAC-SFM was loaded into calcium phosphate bone cement to test the drug release properties in vitro. MC3T3-E1 osteoblasts were cultured on the surface of NAC-SFM calcium phosphate bone cement and cell attachment and growth were observed by scanning electron microscope. Additionally, MC3T3-E1 cells were cultured with three kinds of bone cement extracts (calcium phosphate cement, SFM-calcium phosphate cement, NAC-SFM-calcium phosphate cement, as well as cultured in the α-minimum essential medium containing a volume fraction of 10% fetal bovine serum and 1% penicillin-streptomycin double antibody as the control. MTS assay was used to evaluate cell proliferation. RESULTS AND CONCLUSION: Microspheres in the composite bone cement presented with smooth surface, same size, diffused distribution and no obvious destroy. Thus, the SFM could remain stable in the reaction process of the composite bone cement. The double slow release system which contained silk fibroin microspheres and calcium phosphate bone cement showed a significant decrease in the cumulative release percentage of NAC within the first 24 hours compared with the control group (P < 0.05). In the next 28 days, the release speed of NAC was significantly lower in the NAC-SFM-calcium phosphate cement group than the calcium phosphate cement group (P < 0.05). In addition, different extracts had no significant cytotoxicity to the growth of MC3TC-E1 cells. Thus, the NAC-SFM-calcium phosphate cement has good cytocompatibility, which provide a new insight into the development of bone repair biomaterials. 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Improved injectability and in vitro degradation of a calcium phosphate cement containing poly(lactide-co-glycolide) microspheres

An injectable calcium phosphate cement (CPC) containing 30 wt.% poly(lactide-co-glycolide) (PLGA) microspheres was developed in the present study. Sodium citrate solution was used as the cement liquid phase. The effects of sodium citrate concentration on the injectability, rheological properties, mechanical strength and self-setting properties of CPC containing PLGA microspheres were systematically investigated. The in vitro degradation behavior of the composite during immersion in phosphate buffer solution was also studied. With an increase in sodium citrate concentration, the viscosity and yield stress of the paste were reduced, thereby improving the injectability. At a sodium citrate concentration of 15%, the injectability of the paste reached 95%. The compressive strength of the specimen was also enhanced by the addition of sodium citrate. The specimens had a compressive strength of 32.24+/-2.72 MPa at 15% sodium citrate concentration, compared to 22.15+/-3.60 MPa for the specimen without sodium citrate. The in vitro degradation results demonstrate that incorporated PLGA microspheres can provide the required high strength to CPC in the early stage, which would gradually degrade to create macropores for bone ingrowth. In conclusion, an in situ macropore-generable CPC exhibited excellent injectability and high early strength, and should be a promising material for bone repair and bone reconstruction.     

In vitro ageing of brushite calcium phosphate cement

In vivo studies investigating the use of brushite cements have demonstrated mixed results with one or more of dissolution, hydrolysis, fragmentation and long term stability being demonstrated. It has been suggested that sample volume, implant location, and species can affect in vivo behaviour. As few in vitro studies on this cement system have been performed, this study aimed to compare the effects of static and dynamic in vitro ageing protocols on the phase composition, weight loss and mechanical properties of brushite cement. The effects of immersion liquid to cement volume ratio (LCVR) and sample volume on phase composition were investigated and comparative in vitro experiments were also performed in foetal bovine serum. It was determined that the weight loss after 28 days was up to seven times higher in serum than in phosphate buffered saline (PBS) and that fragmentation accounted for most of the weight loss observed. Hydroxyapatite was formed in PBS but not in serum when aged in refreshed media at all LCVRs investigated. This study has highlighted that LCVR, media refresh rate and media composition are critical to brushite cement performance. It appears that brushite cement removal from an implant site may be complex and dependent on physiological processes other than simple dissolution. A better understanding of these processes could provide the means to engineer more precise calcium phosphate cement degradation profiles.     

Introduction of enzymatically degradable poly(trimethylene carbonate) microspheres into an injectable calcium phosphate cement

Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polyester with rubber-like properties. Introduction of this polymer into an injectable calcium phosphate bone cement can therefore be used to introduce macroporosity into the cement for tissue engineering purposes as well as to improve mechanical properties. Aim of this study was to investigate calcium phosphate cements with incorporated PTMC microspheres (PTMC CPCs) on their physical/mechanical properties and in vitro degradation characteristics. Therefore, composites were tested on setting time and mechanical strength as well as subjected to phosphate buffered saline (PBS) and enzyme containing medium. PTMC CPCs (12.5 and 25 wt%) with molecular weights of 52.7 kg mol(-1) and 176.2 kg mol(-1) were prepared, which showed initial setting times similar to that of original CPC. Though compression strength decreased upon incorporation of PTMC microspheres, elastic properties were improved as strain-at-yield increased with increasing content of microspheres. Sustained degradation of the microspheres inside PTMC CPC occurred when incubated in the enzymatic environment, but not in PBS, which resulted in an interconnected macroporosity for the 25 wt% composites.     

Amphiphilic peptide-loaded nanofibrous calcium phosphate microspheres promote hemostasis in vivo

Most fatalities from trauma occur due to severe blood loss. There is a need for improved hemostatic biomaterials that can address this problem. The aim of this study was to determine the in vivo efficacy of nanofibrous microspheres (NFM) loaded with hemostatic peptides, specifically ideal amphipathic peptides (IAP) that have been demonstrated to possess both procoagulant and antifibrinolyic activities. We demonstrate that IAP can be coupled to NFM (IAP-NFM) to form matrices that exhibit substantial hemostatic activity. IAP-NFM matrices were compared to a commercial zeolitic hemostatic biomaterial (QuikClot) and have superior efficacy in reducing bleeding in vivo. In both a murine tail transection and a murine hepatic injury model, bleeding times were significantly reduced (P < 0.05) with the use of IAP-NFM as compared with equal masses of either QuikClot or NFM alone, or no treatment. Importantly, histological examination revealed no tissue injury when IAP-NFM or NFM were applied to hepatic lacerations. In contrast, QuikClot caused widespread hepatocyte degeneration and necrosis, with higher average injury zone thickness as determined by semiquantitative analysis. In summary, NFM was able to maintain the pro-coagulant properties of IAP in our preclinical model, caused no observable tissue damage at the site of application and had better performance than QuikClot controls.     

一种可注射体内成孔的磷酸钙骨水泥

背景：磷酸钙骨水泥存在脆性大、抗水溶性(血溶性)差、力学性能不足、降解缓慢等缺点,其临床应用受到一定限制,故需要对其进行改性研究。 目的：制备一种具有一定强度、孔隙率、适合骨生长的多孔磷酸钙骨水泥生物支架材料。 方法：以磷酸钙骨水泥为基本体系,液相采用壳聚糖的弱酸溶液,以提高磷酸钙骨水泥的可塑性和黏弹性,使骨水泥具有可注射性,显著提升骨水泥的应用范围及应用舒适度。固相为双相磷酸钙(磷酸四钙+磷酸氢钙)粉体,并在固相中添加一定量的甘露醇及聚乳酸-乙醇酸共聚物作为造孔剂,制备磷酸钙支架材料。 结果与结论：此材料孔径可达到10~300 μm。添加60%致孔剂时,磷酸钙骨水泥固化体孔隙率可达到(68.3±1.5)%。磷酸钙骨水泥孔隙率的增加使材料的力学性能下降,其抗压强度从最初不含致孔剂时的(53.0±1.4) MPa下降到含60%致孔剂的(2.5±0.2) MPa。实验制备的此种多孔磷酸钙骨水泥材料,是具有一定抗压强度、较好的孔隙率,并能体内降解的可注射生物支架材料。     

In vivo degradation of low temperature calcium and magnesium phosphate ceramics in a heterotopic model

Bone replacement using synthetic and degradable materials is desirable in various clinical conditions. Most applied commercial materials are based on hydroxyapatite, which is not chemically degradable under physiological conditions. Here we report the effect of a long-term intramuscular implantation regime on the dissolution of various low temperature calcium and magnesium phosphate ceramics in vivo. The specimens were analysed by consecutive radiographs, micro-computed tomography scans, compressive strength testing, scanning electron microscopy and X-ray diffractometry. After 15months in vivo, the investigated materials brushite (CaHPO(4)·2H(2)O), newberyite (MgHPO(4)·3H(2)O), struvite (MgNH(4)PO(4)·6H(2)O) and hydroxyapatite (Ca(9)(PO(4))(5)HPO(4)OH) showed significant differences regarding changes of their characteristics. Struvite presented the highest loss of mechanical performance (95%), followed by newberyite (67%) and brushite (41%). This was accompanied by both a distinct extent of cement dissolution as well as changes of the phase composition of the retrieved cement implants. While the secondary phosphate phases (brushite, newberyite, struvite) completely dissolved, re-precipitates of whitlockite and octacalcium phosphate were formed in either particulate or whisker-like morphology. Furthermore, for the first time the possibility of a macropore-free volume degradation mechanism of bioceramics was demonstrated.     

复合N-乙酰半胱氨酸丝素蛋白磷酸钙骨水泥的理化性能及细胞毒性

BACKGROUND: Calcium phosphate cements (CPCs) possess the bio-degradation and osteoconduction, and its final hydration product, hydroxyapatite, is the main inorganic constituent of bones. However, its poor mechanical property makes it unable to be used for repairing weight-bearing bone defects. OBJECTIVE: To develop a kind of bioactive bone cements with decent biomechanical property and biocompatibility. METHODS: 6% silk fibroin aqueous solutions containing different concentrations of N-acetylcysteine (0, 10 and 25 mmol/L) were prepared. Each cement sample was prepared by mixing the curing liquid and α-tricalcium phosphate powder with the ratio of 0.4 mL: 1 g; α-tricalcium phosphate powder mixed with ddH2O as control group. The compressive strength, setting time of the cements were measured. The crystal components of the cements were characterized using X-ray diffraction and the microstructure was observed using scanning electron microscope. MC3T3-E1 cells were seeded onto the material in each group, and cell morphology was observed under scanning electron microscope at 24 hours. MC3T3-E1 cells were cultured in the extract of each material, cell proliferation was detected at 1, 3, 5 and 7 days, and the lactate dehydrogenase level was detected at 1 and 3 days. RESULTS AND CONCLUSION: X-ray diffraction and scanning electron microscope showed that the final hydration products of α-tricalcium phosphate in all specimens were hydroxyapatite. When the concentration of N-acetylcysteine was 25 mmol/L, the compressive strength of the material reached (49.39±1.68) MPa, with the initial setting time of (21.77±1.07) minutes and the final setting time of (31.88±1.69) minutes. There was no significant difference in cell morphology among cements. These results suggest that the cement containing N-acetylcysteine exhibites good biocompatibility and high mechanical strength.     

In vivo cell interactions with calcium phosphate bioceramics

Biointegration, resorption process, and solubility in physiological environments of calcium phosphate materials are scarcely described by ultrastructural studies. In vivo cells interactions with calcium phosphate materials are scarcely described by ultrastructural studies. In vivo cells interactions with calcium phosphate biomaterials are mediated by different proteins from physiological fluid, and in order to observe at the ultrastructural level the cell colonization, the resorption, process and the biointegration, we used in these experiments calcium phosphate materials precoated with fibronectin or not precoated. Two kinds of well determined materials were used for this study, Beta-tricalcium phosphate (B-TCP) and hydroxyapatite (HAP). The implants were soaked in human fibronectin diluted solution and were implanted in the connective tissue of rabbit abdomen. Our results showed that the fibroblasts and macrophagous++ cells interaction with the calcium phosphate crystal (B-TCP and HAP) was more important in the experiments with a fibronectin bilayer. In the presence of fibronectin at the grains surface of the material, cystic cavities' or fibrous encapsulation was suppressed and cells with fibers were in close contact with the material. The presence of fibronectin immediately after implantation seemed to increase the adhesion and the cell colonization. Fibronectin creates an organic interface between crystals and cells, and can promote interactions from cells and biomaterials.     

Porous hydroxyapatite and gelatin/hydroxyapatite microspheres obtained by calcium phosphate cement emulsion

Hydroxyapatite and hybrid gelatine/hydroxyapatite microspheres were obtained through a water in oil emulsion of a calcium phosphate cement (CPC). The setting reaction of the CPC, in this case the hydrolysis of α-tricalcium phosphate, was responsible for the consolidation of the microspheres. After the setting reaction, the microspheres consisted of an entangled network of hydroxyapatite crystals, with a high porosity and pore sizes ranging between 0.5 and 5 μm. The size of the microspheres was tailored by controlling the viscosity of the hydrophobic phase, the rotation speed, and the initial powder size of the CPC. The incorporation of gelatin increased the sphericity of the microspheres, as well as their size and size dispersion. To assess the feasibility of using the microspheres as cell microcarriers, Saos-2 cells were cultured on the microspheres. Fluorescent staining, SEM studies, and LDH quantification showed that the microspheres were able to sustain cell growth. Cell adhesion and proliferation was significantly improved in the hybrid gelatin/hydroxyapatite microspheres as compared to the hydroxyapatite ones.     

联合钙盐骨水泥及可降解网状微孔球囊椎体成形的体外实验

背景：椎体成形、椎体后凸成形治疗骨质疏松性椎体压缩性骨折中存在骨水泥外溢、伤椎及临近椎体继发骨折等风险。 目的：验证高分子可降解网状微孔球囊应用于骨质疏松性椎体压缩骨折的可行性。 方法：以聚乳酸-已内酯共聚物为原材料,采用静电纺丝技术制备可降解网状微孔球囊,同时制备涂层球囊,扫描电镜观察其形貌;向球囊内分别注入水和骨水泥,观察外渗情况;测试球囊的断裂强度和断裂伸长率。采用细胞染色法和CCK-8法测试小鼠胚胎成骨细胞在两种球囊上的增殖情况。观察两种球囊在模拟体液、猪胰脂肪酶溶液和新鲜的人血清中的降解。将球囊置入猪椎体后测试球囊的爆破压。将钙盐骨水泥注入球囊后密封,固化后置于6 atm压力的超纯水中,定期检测钙离子浓度。 结果与结论：网状微孔球囊具有良好的纤维形态,粗细分布均匀,存在孔隙;涂层球囊表面无具体形态结构及孔隙存在。与涂层球囊相比,网状微孔球囊具有更好的力学性能和液体渗透性及爆破压力,可防止骨水泥渗漏,促进成骨细胞的黏附与增殖,降解更均匀、稳定,可较好保持钙离子浓度,更利于新骨生长和骨折愈合。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

In vivo performance of biodegradable calcium phosphate glass ceramics using the rabbit model: histological and SEM observation

Two MK5 (45CaO-45P(2)O(5)-5MgO-5K(2)O, in mol%) and MT13 (45CaO-37P(2)O(5)-5MgO-13TiO(2), in mol%) glasses are prepared in the meta- and pyrophosphate regions and crystallized to obtain MK5B and MT13B, respectively. MK5B was obtained by controlled crystallization, and MT13B by powder sintering. As a result of these heat treatment processes, the crystalline phases precipitated in the glassy matrix are KCa(PO(3))(3), beta-Ca(PO(3))(2), beta-Ca(2)P(2)O(7) and Ca(4)P(6)O(19) phases for MK5B and CaTi(4)(PO(4))(6), TiP(2)O(7), alpha- and beta-Ca(2)P(2)O(7) phases for MT13B. To assess the in vivo biological behavior of these glass ceramics, a mixed granulometry in the range 250-355 mum and 355-425 mum with a ratio of 1/1 was implanted for 2, 4, and 12 weeks in the tibiae of Japanese white rabbits. The results showed that the in vivo behavior was strongly affected by their solubility. All implanted materials, MK5B and MT13B, and beta-tricalcium phosphate (beta-TCP) as control material, showed signs of degradation in vivo. However, the levels of degradation were quite different throughout the implantation periods. The highest degradation was observed for MK5B glass ceramic and the lowest for MT13B with beta-TCP in-between. All implanted materials allow for new bone formation in the bone defect area. At the longest implantation period (12 weeks), the MT13B and beta-TCP materials were almost completely surrounded by new bone tissue, whereas MK5B showed some unfilled spaces. This behavior is discussed in terms of the high degradation observed in previous studies.